Transcript Study Closure

Study Closure
What Happens Next?
USF and TGH Research Coordinator's Meeting: November 16 & 17, 2016 || Emily Dayton, TGH Clinical Research Coordinator
Objectives

Review key steps for study coordinator at study
closure

Identify Responsibilities of
 Sponsor
 PI
 Site
 IRB
Staff
Study Closure

Follow your institutional policies regarding study close-out

The official study end date is established by the IRB closure letter

Department administrators must communicate with their study teams
to ensure that they are aware when a site is in the closeout phase of a
study. All administrative and fiscal responsibilities pertaining to the
study should be accomplished prior to the official end date of the
study (date of IRB closure letter).
Information obtained from e-mail correspondence from Caroline Holt, “Study End Dates” 11/2/2016.
Study Closure, continued

Study coordinators must inform their departmental administrators
when an application is being submitted for IRB closure

Responsibilities include but are not limited to:

Updating payroll distribution

Updating blanket POs

Closing all unliquidated POs

Change of chartfield string on any recurring charges (telephone, etc).

Study coordinators should inform the pharmacy of pending study closure in a
timely manner so the pharmacy will discontinue generating invoices for the
study drug

This is a critical step as fees will no longer be waived
Information obtained from e-mail correspondence from Caroline Holt, “Study End Dates” 11/2/2016.
Sponsor Responsibility

Provide final clinical study report to investigator/institutions as well
as to the IRB. (FDA, 1996, p. 37)


Should also ensure that the reports in marketing applications meet the
standards of the ICH Guidance for Structure and Content of Clinical Study
Reports
Advise the site when records can be destroyed

This does not always happen but it could!
FDA: U.S. Food & Drug Administration. (1996, April). ICH E6: Good Clinical Practice: Consolidated Guidance. Retrieved from Science & Research: ICH
Guidance Documents: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf
Sponsor Responsibilities: 21 CFR 312
Sec. 312.57 Recordkeeping and record retention.
(a) A sponsor shall maintain adequate records showing the receipt, shipment, or other disposition of the
investigational drug. These records are required to include, as appropriate, the name of the investigator
to whom the drug is shipped, and the date, quantity, and batch or code mark of each such shipment.
(b) A sponsor shall maintain complete and accurate records showing any financial interest in 54.4(a)(3)(i),
(a)(3)(ii), (a)(3)(iii), and (a)(3)(iv) of this chapter paid to clinical investigators by the sponsor of the covered
study. A sponsor shall also maintain complete and accurate records concerning all other financial interests of
investigators subject to part 54 of this chapter.
(c) A sponsor shall retain the records and reports required by this part for 2 years after a marketing
application is approved for the drug; or, if an application is not approved for the drug, until 2 years after
shipment and delivery of the drug for investigational use is discontinued and FDA has been so notified.
(d) A sponsor shall retain reserve samples of any test article and reference standard identified in, and used in
any of the bioequivalence or bioavailability studies described in, 320.38 or 320.63 of this chapter, and release
the reserve samples to FDA upon request, in accordance with, and for the period specified in 320.38.
U.S. Government Publishing Office. (2002, March 4). Title 21: Food and Drugs 312.57 Recordkeeping and record retention. Retrieved from Electronic Code of
Federal Regulations: http://www.ecfr.gov/cgi-bin/text-idx?SID=74b4f315e3274fd653d6507f10cd82f6&mc=true&node=se21.5.312_157&rgn=div8
PI Responsibility

Submit financial disclosure (FDF) to the sponsor 1 year following study
completion (21 CFR 54.6)

More information on this can be found in the Guidance for Clinical Investigators,
Industry, and FDA Staff: Financial Disclosure by Clinical Investigators (link provided
in “resource” slides).

Keep records accessible so they can be retrieved if requested

Maintain records for:
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2 years following the date a marketing application is approved for the drug for the
indication for which it is being investigated
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2 years after the investigation is discontinued and FDA is notified if no application
is to be filed or if the application has not been approved for such indication
Site Staff Responsibility

Ultimately the investigator is responsible for study documents.

Site staff should provide support to their investigator while following
federal regulations and guidelines as well as institutional policies.

Institutional policies may require you to retain documents longer than specified by
federal regulations and guidance.
IRB Responsibility

The IRB must retain records for a minimum of 3 years after study
closure/completion. (21 CFR 56.115(b))


These documents must be available for inspection by authorized representatives of
the FDA at reasonable times and in a reasonable manner.
USF HRPP Policy and Procedure Manual outlines the IRB’s Responsibility in
section 19.2, Records and Retention Accessibility.

This policy follows:

21 CFR 56.115(b) and 45 CFR 46.115(b)

Florida Statues §119 and §286
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USF System Policy 5-012
Scenarios: What do I do?
Photo permission and credit: Emily Dayton, 10 Nov. 2016
The study has been closed for 2 years and the
PI is no longer at my site, what do I do?

Read your Clinical Trials Agreement

Read your institutional policies

Reference HHS regulations (45 CFR 46.115(b).)


See next slide
Take home note: The records can be transferred to another
investigator at the site or the someone at the site can assume
responsibility of maintaining the records. The PI or site is responsible
for notifying the sponsor who at the site is responsible for
maintaining the records.
Photo permission and credit: Emily Dayton 10 Nov. 2016
“
If investigators who have been designated to retain records on
behalf of the institution leave that institution, the investigators
and the institution should identify the successor responsible for
maintaining those institutional records, either at the original
institution or wherever the records are relocated, for the period
of time required under HHS regulations at 45 CFR 46.115(b).
Office for Human Research Protections
Office for Human Research Protections. (n.d.). Investigator Responsibilities FAQ. Retrieved from U.S. Department of Health & Human Services:
http://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/investigator-responsibilities/#
”
Clinical Trials Agreement

Often the CTA details the expectation for record maintenance and
retention
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Examples could include:

At least 2 years after the last approval of marketing application for the
device/compound in the United States, European Union, Japan, and India.

This could be a really long time!

2 years following notification from sponsor that it has formally discontinued
clinical development

Institution will notify sponsor prior to destruction of any trial-related records
and, if requested by sponsor, shall transfer such records to sponsor at sponsor’s
expense.
We started the study start-up process but
never opened the trial at our site; what are
my next steps?

If the start-up ceased prior to IRB approval, follow your institutional policies
on record retention.

If you received IRB approval and did not open the trial at your site you must
close the study with the IRB.


IRB documents must be retained for a minimum of 3 years according to federal
regulations and guidelines; follow your institutional or IRB policy if required
retention is longer.
If requested by the sponsor, you can transfer documents to them at their
expense.

This is usually outlined in the CTA if one was signed.
Resources

Electronic Code of Federal Regulations

Title 21 Part 312: Investigational New Drug Application


Title 21 Part 812: Investigational Device Exemptions


http://www.ecfr.gov/cgi-bin/textidx?SID=afd7a85f06174b1115c804874be0bec8&mc=true&tpl=/ecfrbrowse/Title21/21cfr312
_main_02.tpl
http://www.ecfr.gov/cgi-bin/textidx?SID=afd7a85f06174b1115c804874be0bec8&mc=true&tpl=/ecfrbrowse/Title21/21cfr812
_main_02.tpl
Title 45 Part 46: Protection of Human Subjects

http://www.ecfr.gov/cgi-bin/textidx?SID=afd7a85f06174b1115c804874be0bec8&mc=true&tpl=/ecfrbrowse/Title45/45cfr46_
main_02.tpl
More Resources


FDA’s 2013 Clinical Investigator Training Course

This is a PowerPoint with a lot of useful information regarding the Investigator and
Sponsor roles and responsibilities as well as information regarding
inspections/audits conducted by a regulatory authority

http://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM37
8565.pdf
Guidance for Clinical Investigators, Industry, and FDA Staff: Financial
Disclosure by Clinical Investigators

http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM341008.pdf
USF and TGH Research Coordinator's Meeting: November 16 & 17, 2016 || ed
Resources, continued

USF HRPP Policy and Procedure Manual & Regulation and Guidance

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USF and TGH Research Coordinator's Meeting: November 16 & 17, 2016 || ed
References
FDA: U.S. Food & Drug Administration. (1996, April). ICH E6: Good Clinical Practice: Consolidated Guidance. Retrieved from
Science & Research: ICH Guidance Documents:
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm073122.pdf
Office for Human Research Protections. (n.d.). Investigator Responsibilities FAQ. Retrieved from U.S. Department of Health &
Human Services: http://www.hhs.gov/ohrp/regulations-and-policy/guidance/faq/investigator-responsibilities/#
U.S. Government Publishing Office. (2002, March 4). Title 21: Food and Drugs 312 Investigational New Drug Application.
Retrieved from Electronic Code of Federal Regulations: http://www.ecfr.gov/cgibin/retrieveECFR?gp=&SID=13d6f2db34c2f722eb87e4771c73ab61&mc=true&n=pt21.5.312&r=PART&ty=HTML
U.S. Government Publishing Office. (2002, March 4). Title 21: Food and Drugs 312.57 Recordkeeping and record retention.
Retrieved from Electronic Code of Federal Regulations: http://www.ecfr.gov/cgi-b
in/textidx?SID=74b4f315e3274fd653d6507f10cd82f6&mc=true&node=se21.5.312_157&rgn=div8
Thank you!
Emily Dayton
Clinical Research Coordinator
Tampa General Hospital
Office of Clinical Research
813-844-3802
[email protected]
Please do not redistribute or copy without written permission. All photos shared with verbal parental permission.